Alkali-treated coca is commonly used in areas of food deprivation, e.g., coca chewing in the Andes, where the main dietary staple is high-carbohydrate foodstuffs. There is good evidence that malnutrition and associated problems of hypoglycemia and malabsorption are wide-spread in these areas. Whether any of the biological effects of coca help to maintain or disrupt physiological homeostasis particularly with regard to overall body metabolism is very much an unsettled issue of the "coca problem". Also unresolved is the issue of whether the overall biological effects associated with the use of coca are due to cocaine or its metabolites, or some substance released by the alkali treatment of the coca, e.g. ecgonine. Complicating the various issues of the "coca problem" is the conspicuous lack of basic information on the disposition of cocaine ingested orally. The present proposal includes experiments addressing themselves to these issues. The experiments are designed: (1st) To characterize the pharmacokinetic profiles of cocaine, benzoyl ecgonine and ecgonine in the dog, after administering each test substance intravenously and intragastrically (orally) in order to evaluate the overall biotransformation of cocaine with particular regard to the importance of intestino-hepatic first-pass effects in the metabolism of oral cocaine. (2nd) To study in vitro the kinetics of the chemical conversion of cocaine to benzoyl ecgonine and/or ecgonine to determine the optimum conditions for the reaction. (3rd) To study the possible effects of cocaine, benzoyl ecgonine and ecgonine on carbohydrate (xylose) absorption and on the relative utilization of fats and carbohydrates in the rat at different levels of nutrition.